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Synergistic Effects of Natural Product Combinations in Protecting the Endothelium Against Cardiovascular Risk Factors.

ABSTRACT: Endothelial dysfunction is an early hallmark of cardiovascular diseases (CVDs). Monotherapies are limited due to the complex, multifactorial pathways. The multi-component and multi-targeted approach of natural products have the potential to manage CVDs.This review aims to provide a comprehensive insight into the synergistic mechanism of natural product combinations in protecting the endothelium against various cardiovascular risk factors.Databases (PubMed, MEDLINE and EMBASE) and Google Scholar were searched, and studies in English published between January 2000 and February 2022 were collated. Clinical and pre-clinical studies of natural product combinations with or without pharmaceutical medicines, compared with monotherapy and/or proposing the underlying mechanism in protecting endothelial function, were included.Four clinical studies demonstrated that natural product combinations or natural product-pharmaceutical combinations improved endothelial function. This was associated with multi-targeted effects or improved absorption of the active substances in the body. Seventeen preclinical studies showed that natural product combinations produced synergistic (demonstrated by combination index or Bliss independence model) or enhanced effects in protecting the endothelium against hyperlipidemia, hypertension, diabetes mellitus, platelet activation, oxidative stress and hyperhomocysteinemia. The molecular targets included reactive oxygen species, Nrf2-HO-1, p38MAPK, P13K/Akt and NF-κB.Thus, the current available evidence of natural product combinations in targeting endothelial dysfunction is predominantly from preclinical studies. These have demonstrated synergistic/enhanced pharmacological activities and proposed associated mechanisms. However, evidence from larger, well-designed clinical trials remains weak. More cohesion is required between preclinical and clinical data to support natural product combinations in preventing or slowing the progression of CVDs.

SUBMITTER: Yousaf M

PROVIDER: S-EPMC9297466 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Natural antimicrobials (NAM) are promising candidates for the successful control of poultry-borne bacteria, carrying potent antimicrobial activity (AMA) against a wide range of multidrug-resistant pathogens. Individual activities of carvacrol, eugenol, trans-cinnamaldehyde, oregano, and thymol, along with the combined activity of paired compounds, were examined using broth microdilution and checkerboard techniques. The characteristic interactions between the compounds were calculated using an improved method, based on combination index (CI) values. The bacteria examined herein were selected due to their known genetic resistance to at least one antibiotic. Our results indicated that thymol was most effective, exhibiting the lowest minimum inhibitory concentration (MIC) value against Salmonella pullorum, Escherichia coli, and Klebsiella pneumoniae, establishing the order of antimicrobial efficacy as: thymol > oregano > carvacrol > trans-cinnamaldehyde > eugenol. In the interaction study, the paired combination of carvacrol and thymol showed synergistic effects and was highly effective in reducing the antibiotic resistance of all the evaluated pathogens. Notably, all CI values were <1.0 in evaluations of S. pullorum, indicating the absence of antagonism between eugenol and thymol (or oregano). In K. pneumoniae, majority of CI values, which had a few concentration points, were smaller than 1.0, indicating a synergistic effect between eugenol and carvacrol (oregano or thymol), and trans-cinnamaldehyde and carvacrol. In E. coli, apart from some concentration points, some CI values were smaller than 1.0, demonstrating a synergistic effect between eugenol and carvacrol, and thymol and carvacrol (eugenol or oregano). It is therefore of great significance to investigate and illuminate the minimal effect concentration of these five components when they are used in combination as feed additives. Moreover, the improved evaluation method of this study provides a precise and extensive means to assess the synergistic effects of NAM.

Project description:Background and Objectives: Developing effective treatment outcomes for multidrug-resistant Acinetobacter baumannii (MRAB) infections, with colistin and tigecycline the current frontline therapies, is challenging, because of the risk of renal toxicity and low blood concentrations of active ingredients when administered intravenously. This study aimed to identify the effect of combination therapy using conventional antimicrobial agents that are used for treating drug-resistant bacteria and the additional synergistic effect of four probiotic culture extracts isolated from the human body and Lactobacillus preparations. Materials and Methods: The antimicrobial combination and synergistic effect of adding Lactobacillus extract against 33 strains of A. baumannii isolated from pus, urine, and other specimens submitted to the Department of Laboratory Medicine of a university hospital, located in Gyeonggi-do, Korea, was investigated over a 3-year period between January 2017 and December 2019. Results: Antimicrobial susceptibility tests on bacteria isolated in clinical practice demonstrated that 26 strains (79%) were MRAB, while multi-locus sequence typing indicated that ST191 was the predominant type (45%; n = 15). Checkerboard test results demonstrated that combination therapy using meropenem and colistin had the highest synergistic effect (fractional inhibitory concentration index = 0.5), while the time-kill assay test using Lactobacillus spp. culture extract exhibited an inhibitory effect within 1 h and complete inhibition of MRAB within 3 h. Lactobacillus paracasei exhibited the fastest antimicrobial reactivity and longest sustained antimicrobial activity. Conclusion: These findings provide useful foundational data for an appropriate combination of colistin with other antimicrobial agents for treating MRAB infection in clinical settings, and the use of various probiotic culture extracts to reduce the required dosage, and therefore toxicity of colistin.

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Synergistic Effects of Natural Product Combinations in Protecting the Endothelium Against Cardiovascular Risk Factors.

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